Info

11 [7-15]

35 [28-42]

40 [33-47]

43 [35-51]

The HLA class II DPB1 locus (see Fig. 1) may also influence susceptibility to T1DM. Analysis of 269 multiplex families from the Human Biological Data Interchange suggest that HLA-DPB 1*0301 and HLA-DPB1 *0202 alleles are predisposing for T1DM, whereas HLA-DPB1*0402 appears protective (115). Interestingly, the effect of the class II locus DPB1 appears to be more apparent in patients with this genotype than in patients carrying the highest-risk DR3/DR4-DQB1*0302 genotype (115).

Fig. 6. The human TCR P-chain locus on chromosome 7 encompasses 75 different variable segments, each with its own leader sequence (VP1-VP« and L1-Lw). These are associated with two gene clusters, one composed of one diversity segment (Dpi), six joining segments (JP11 ••• 6), and one constant segment (CP1) encoding the p1-chain, and the other with the DP2/DP21 ••• 6/CP2 segment encoding the P2 chain. Two somatic recombination events take place to generate the version of the rearranged DNA that is eventually transcribed. The D-J joining event occurs first, followed by the V-D-J event. The rearranged DNA is then transcribed into the primary RNA transcript. This transcript is converted into messenger RNA (mRNA) through an RNA splicing event. The TCR P-chain protein will be made after translation, processing, and glycosylation. The leader sequence is removed once the TCR P-chain is in place on the cell membrane. (Modified from ref. 51.)

Fig. 6. The human TCR P-chain locus on chromosome 7 encompasses 75 different variable segments, each with its own leader sequence (VP1-VP« and L1-Lw). These are associated with two gene clusters, one composed of one diversity segment (Dpi), six joining segments (JP11 ••• 6), and one constant segment (CP1) encoding the p1-chain, and the other with the DP2/DP21 ••• 6/CP2 segment encoding the P2 chain. Two somatic recombination events take place to generate the version of the rearranged DNA that is eventually transcribed. The D-J joining event occurs first, followed by the V-D-J event. The rearranged DNA is then transcribed into the primary RNA transcript. This transcript is converted into messenger RNA (mRNA) through an RNA splicing event. The TCR P-chain protein will be made after translation, processing, and glycosylation. The leader sequence is removed once the TCR P-chain is in place on the cell membrane. (Modified from ref. 51.)

The prevalence of HLA-DR2 is decreased (116,117) in patients with T1DM, and the DQA1*0102/DQB1*0502/DRB 1*1601 haplotype accounts for the most part of disease susceptibility in DR2-associated cases of T1DM (118-123). Therefore, the originally described effect of the DR2 allele in conferring resistance to diabetes is considered to be neutral rather than protective, whereas the real protective effect is provided by the DQ alleles, generally found in linkage disequilibrium with DR2. The effects of HLA alleles on T1DM susceptibility are summarized in Table 6.

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